5-Animals: New generation of GE-pigs with extra growth hormon genes announced

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Subject: 5-Animals: New generation of GE-pigs with extra growth hormon genes announced

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Date: Wed, 15 Mar 2000 12:58:27 +0100

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----------------------------- GENET-news -----------------------------
TITLE: Modified genes stimulate pig growth
SOURCE: ISB News Report - March 2000
by Eric A. Wong
DATE: March 3, 2000
-------------------- archive: http://www.gene.ch/ --------------------
Modified genes stimulate pig growth
The growth hormone, secreted by the pituitary, plays a key role in
regulating growth and metabolism in mammals. Under normal conditions,
growth hormone (GH) secretion is regulated by two hypothalamic
hormones. Growth hormone releasing hormone (GHRH) stimulates GH
secretion, while somatostatin inhibits GH secretion. The secreted GH
induces the synthesis and secretion of insulin-like growth factor-I
(IGF-I) mainly from the liver into the blood. IGF-I then acts at a
number of target tissues to stimulate growth.
Transgenesis has been previously investigated as a method of
increasing growth rate in pigs. In the late 1980s, transgenic pigs
containing a human or bovine GH gene under the control of the liver-
specific metallothionein promoter showed increased weight gain,
increased feed efficiency, and decreased fat deposition. A number of
pathologies, however, were also observed in these GH-transgenic pigs
such as gastric ulcers, arthritic joints, and decreased libido. In an
attempt to circumvent these problems, transgenic pigs secreting human
GHRH from the liver were developed. No effect was observed, however,
in these GHRH-transgenic pigs, perhaps due to breakdown of the GHRH
in the circulation by peptidases.
A different approach for overexpression of GHRH in pigs is reported
in the December 1999 issue of Nature Biotechnology. Researchers at
Baylor College of Medicine and Penn State combined the technologies
of site-directed mutagenesis and electrogene therapy (direct plasmid
gene transfer plus electroporation) to express a protease-resistant
GHRH in transfected muscle tissue of pigs.
A DNA construct containing the porcine GHRH gene under the control of
a muscle-specific synthetic promoter was constructed. A single 10 mg
dose of this plasmid was injected intramuscularly into three week old
piglets. To improve the efficiency of cellular uptake of the plasmid
DNA, a pair of electrodes were then inserted into the DNA injection
site to deliver electric pulses. These injected pigs showed a two- to
four-fold increase in serum GHRH, an increase in GH secretion, and a
three- to six-fold increase in serum IGF-I. The increases in serum
GHRH and IGF-I were maintained for over 60 days after injection.
The myogenic overexpression of porcine GHRH increased growth over 65
days. Pigs injected with the modified porcine GHRH on average were
42% heavier than controls at 62 days (42 kg versus 29 kg). Body
composition studies showed a proportional increase of all body
components in GHRH injected animals. No signs of organomegaly or
associated pathology were observed. Feed conversion in GHRH injected
animals improved by 20% over controls. A significant reduction in
serum urea concentration was reported indicating a decrease in amino
acid catabolism.
These results demonstrate a promising, simple, and inexpensive
approach for increasing growth rate in swine with no apparent adverse
side effects. Only a single injection of naked plasmid DNA encoding a
modified GHRH gene into muscle is effective. It will be interesting
to see if this increase in growth rate can persist for six months
until pigs reach the typical market weight of 110 to 120 kg.
Source
Draghia-Akli R et al. 1999. Myogenic expression of an injectable
protease-resistant growth hormone-releasing hormone augments long
term growth in pigs. Nature Biotechnology 17: 1179-1183.
Eric A. Wong
Department of Animal and Poultry Sciences
Virginia Tech
ewong@vt.edu
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